Abstract
Despite considerable progress in preventing mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), eliminating paediatric HIV has not been achieved. Extended postnatal prophylaxis (ePNP), defined as prophylaxis administered to an HIV-exposed child after PMTCT perinatal prophylaxis ends, has been evaluated and is now proposed as an improved approach towards elimination. This approach should be urgently incorporated into international PMTCT recommendations. The antiretroviral drugs most commonly studied as ePNP, either alone or in combination, are lamivudine, nevirapine, lopinavir/ritonavir and zidovudine. In this study, we examined the efficacy, safety, pharmacology, genetic barrier to resistance and practicality of various ePNP regimens. Regimens combining multiple antiretroviral drugs are no more effective than single-drug regimens in terms of protective efficacy but they are associated with increased toxicity. On the basis of these criteria, we recommend lamivudine as the preferred ePNP drug or nevirapine as an alternative. Guided by maternal HIV viral load, ePNP may be particularly indicated, as it could ensure that the prophylaxis provides the greatest benefit/risk to children at highest risk. Long-acting injectable antiretroviral drugs and broadly neutralising antibodies (bNAbs) have yet to be fully evaluated in neonates, infants and children; however, they may offer new alternatives in the future.